Spectroscopic Properties of Protein‐Bound Cofactors: Calculation by Combined Quantum Mechanical/Molecular Mechanical (
            <scp>QM</scp>
            /
            <scp>MM</scp>
            ) Approaches

Sundararajan, Mahesh; Riplinger, Christoph; Orio, Maylis; Wennmohs, Frank; Neese, Frank

doi:10.1002/0470862106.ia601

Cited by 2 publications

(2 citation statements)

References 104 publications

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“…Here, only a few molecular orientations are excited within individual experiments permitting the reconstruction not only of the magnetic hyperfine tensors but also of their orientations in the molecular frame. Nevertheless, the interpretation of the EPR data in terms of a structure requires the use of sophisticated quantum chemical calculations, as was shown in previous work. − DFT calculations can generate possible molecular structures of the trapped intermediate that serve as a model(s) for the simulation of the EPR data. The calculated EPR parameters can then be employed for the interpretation of the spin-Hamiltonian parameters of the intermediate.…”

Section: Introductionmentioning

confidence: 99%

ENDOR Spectroscopy and DFT Calculations: Evidence for the Hydrogen-Bond Network Within α2 in the PCET of E. coli Ribonucleotide Reductase

et al. 2012

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E.coli class I ribonucleotide reductase (RNR) catalyzes the conversion of nucleotides to deoxynucleotides and is composed of two subunits: α2 and β2. β2 contains a stable di-iron tyrosyl radical (Y122•) cofactor required to generate a thiyl radical (C439•) in α2 over a distance of 35 Å, which in turn initiates the chemistry of the reduction process. The radical transfer process is proposed to occur by proton-coupled electron transfer (PCET) via a specific pathway: Y122 ⇆ W48[?] ⇆ Y356 in β2, across the subunit interface to Y731⇆ Y730 ⇆ C439 in α2. Within α2 a co-linear PCET model has been proposed. To obtain evidence for this model, 3-amino tyrosine (NH2Y) replaced Y730 in α2 and this mutant was incubated with β2, CDP and ATP to generate a (NH2Y730•) in D2O. [2H]-Electron-nuclear double resonance (ENDOR) spectra at 94 GHz of this intermediate were obtained and together with DFT models of α2 and quantum chemical calculations allowed assignment of the prominent ENDOR features to two hydrogen bonds likely associated with C439 and Y731. A third proton was assigned to a water molecule in close proximity (2.2 Å O-H---O distance) to residue 730. The calculations also suggest that the unusual g-values measured for NH2Y730• are consistent with the combined effect of the hydrogen bonds to Cys439 and Tyr731, both nearly perpendicular to the ring plane of NH2Y730. The results provide the first experimental evidence for the hydrogen bond network between the pathway residues in α2 of the active RNR complex, for which no structural data is available.

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Section: Introductionmentioning

confidence: 99%

ENDOR Spectroscopy and DFT Calculations: Evidence for the Hydrogen-Bond Network Within α2 in the PCET of E. coli Ribonucleotide Reductase

et al. 2012

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“…In recent years, there has been a widespread diffusion of QM/MM calculations of structures, reactivity and spectroscopic properties of proteins and enzymes. [48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66] In fact, this strategy assures that the influence of the protein on the geometry of hydrogen bonds and on the spectroscopic parameters is adequately included in the calculations.…”

Section: Introductionmentioning

confidence: 99%

EPR parameters of amino acid radicals in P. eryngii versatile peroxidase and its W164Y variant computed at the QM/MM level

Bernini

Pogni

Ruíz-Dueñas

et al. 2011

Phys. Chem. Chem. Phys.

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Quantum mechanics/molecular mechanics (QM/MM) methods, employing density functional theory (DFT), have been used to compute the electron paramagnetic resonance (EPR) parameters of tryptophan and tyrosyl radical intermediates involved in the catalytic cycle of Pleurotus eryngii versatile peroxidase (VP) and its W164Y variant, respectively. These radicals have been previously experimentally detected and characterized both in the two-electron and one-electron activated forms of the enzymes. In this work, the well-studied W164 radical in VP has been chosen for calibration purposes because its spectroscopic properties have been extensively studied by multifrequency EPR and ENDOR spectroscopies. Using a B3LYP/CHARMM procedure, appropriately accounting for electrostatic, such as hydrogen bonding, and steric environmental interactions, a good agreement between the calculated and measured EPR parameters for both radicals has been achieved; g-tensors, hyperfine coupling constants (hfcc) and Mulliken spin densities have been correlated to changes in geometries, hydrogen bond networks and electrostatic environment, with the aim of understanding the influence of the protein surroundings on EPR properties. In addition, the present calculations demonstrate, for VP, the formation of a neutral tryptophan radical, hydrogen bonded to the nearby E243, via a stepwise electron and proton transfer with earlier involvement of a short-lived tryptophan cationic species. Instead, for W164Y, the QM/MM dynamics simulation shows that the tyrosine oxidation proceeds via a concerted electron and proton transfer and is accompanied by a significant reorganization of residues and water molecules surrounding the tyrosyl radical.

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Spectroscopic Properties of Protein‐Bound Cofactors: Calculation by Combined Quantum Mechanical/Molecular Mechanical ( QM / MM ) Approaches

Cited by 2 publications

References 104 publications

ENDOR Spectroscopy and DFT Calculations: Evidence for the Hydrogen-Bond Network Within α2 in the PCET of E. coli Ribonucleotide Reductase

ENDOR Spectroscopy and DFT Calculations: Evidence for the Hydrogen-Bond Network Within α2 in the PCET of E. coli Ribonucleotide Reductase

EPR parameters of amino acid radicals in P. eryngii versatile peroxidase and its W164Y variant computed at the QM/MM level

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